A5073776710- Cancer Genomics and Diagnostics
- Cancer Cells and Metastasis
- Breast Cancer Treatment Studies
- Cancer Immunotherapy and Biomarkers
- Epigenetics and DNA Methylation
- Genetic factors in colorectal cancer
- Single-cell and spatial transcriptomics
- Ferroptosis and cancer prognosis
- Molecular Biology Techniques and Applications
- Genomics and Chromatin Dynamics
- Cancer-related molecular mechanisms research
- Nutrition, Genetics, and Disease
- Advanced Breast Cancer Therapies
- Lung Cancer Treatments and Mutations
- Neurobiology and Insect Physiology Research
- Gene expression and cancer classification
- Genetics, Aging, and Longevity in Model Organisms
- Physiological and biochemical adaptations
- Genetic Associations and Epidemiology
- Cancer, Hypoxia, and Metabolism
- Cell Image Analysis Techniques
- HER2/EGFR in Cancer Research
- Biomimetic flight and propulsion mechanisms
- Prostate Cancer Treatment and Research
- Dietary Effects on Health
University of California, San Francisco
2019-2025
UCSF Helen Diller Family Comprehensive Cancer Center
2019-2025
Cyclotron (Netherlands)
2022-2024
Lawrence Berkeley National Laboratory
2017-2024
Beckman Research Institute
2018-2024
City of Hope
2017-2024
City Of Hope National Medical Center
2021
California Institute of Technology
2003-2013
ETH Zurich
2003
Using three-dimensional infrared high-speed video, we captured the wing and body kinematics of free-flying fruit flies as they performed rapid flight maneuvers. We then "replayed" on a dynamically scaled robotic model to measure aerodynamic forces produced by wings. The results show that fly generates turns with surprisingly subtle modifications in motion, which nonetheless generate sufficient torque for rotate its through each turn. magnitude time course motion during indicate inertia, not...
Using pre-treatment gene expression, protein/phosphoprotein, and clinical data from the I-SPY2 neoadjuvant platform trial (NCT01042379), we create alternative breast cancer subtypes incorporating tumor biology beyond hormone receptor (HR) human epidermal growth factor receptor-2 (HER2) status to better predict drug responses. We assess predictive performance of mechanism-of-action biomarkers ∼990 patients treated with 10 regimens targeting diverse biology. explore >11 subtyping schemas...
The lack of multi-omics cancer datasets with extensive follow-up information hinders the identification accurate biomarkers clinical outcome. In this cohort study, we performed comprehensive genomic analyses on fresh-frozen samples from 348 patients affected by primary colon cancer, encompassing RNA, whole-exome, deep T cell receptor and 16S bacterial rRNA gene sequencing tumor matched healthy tissue, complemented whole-genome for further microbiome characterization. A type 1 helper cell,...
Circulating tumor DNA (ctDNA) analysis may improve early-stage breast cancer treatment via non-invasive burden assessment. To investigate subtype-specific differences in the clinical significance and biology of ctDNA shedding, we perform serial personalized hormone receptor (HR)-positive/HER2-negative triple-negative (TNBC) patients receiving neoadjuvant chemotherapy (NAC) I-SPY2 trial. positivity rates before, during, after NAC are higher TNBC than HR-positive/HER2-negative patients. Early...
SUMMARY Using 3D infrared high-speed video, we captured the continuous wing and body kinematics of free-flying fruit flies, Drosophila melanogaster,during hovering slow forward flight. We then `replayed' on a dynamically scaled robotic model to measure aerodynamic forces produced by wings. Hovering animals generate U-shaped trajectory, in which large drag during downward plunge at start each stroke create peak vertical forces. Quasi-steady mechanisms could account for nearly all mean...
Abstract During aging in the human mammary gland, luminal epithelial cells lose lineage fidelity by expressing markers normally expressed myoepithelial cells. We hypothesize that loss of is a general manifestation epithelia are susceptible to cancer initiation. In present study, we show histologically normal breast tissue from younger women who cancer, as result harboring germline mutation BRCA1 , BRCA2 or PALB2 genes, exhibits hallmarks accelerated aging. These include proportionately...
As animals move through the world in search of resources, they change course reaction to both external sensory cues and internally-generated programs. Elucidating functional logic complex algorithms is challenging because observable actions animal cannot be unambiguously assigned externally- or internally-triggered events. We present a technique that addresses this challenge by assessing quantitatively contribution stimuli internal processes. apply analysis rapid turns ("saccades") freely...
A primary function of DNA methylation in mammalian genomes is to repress transposable elements (TEs). The widespread loss that commonly observed cancer cells results the epigenetic repression TEs. aging process similarly characterized by changes methylome. However, impact these epigenomic alterations on TE silencing and functional consequences this have remained unclear. To assess regulation TEs aging, we profiled human mammary luminal epithelial (LEps)—a key cell lineage implicated...
Abstract Introduction: The tumor immune microenvironment (TME) is a strong prognostic factor in breast cancer with higher proportions of infiltrating lymphocytes associated longer survival. Features the TME vary by race/ethnicity and are linked to disparities outcomes. In 2021, we performed first comprehensive investigation effect germline variants on traits Leveraging pan-cancer data from Cancer Genome Atlas (TCGA), identified 33 heritable >1500 SNPs TME. We hypothesize that...
<title>Abstract</title> Despite efforts to understand breast cancer biology, metastatic disease remains a clinical challenge. Identifying suppressors of progression and mechanisms transition more invasive phenotypes could provide game changing therapeutic opportunities. Transcriptional deregulation is central all malignancies, highlighted by the extensive reprogramming regulatory elements that underlie oncogenic programs. Among these, super-enhancers (SEs) stand out due their enrichment in...
Abstract Background: Predicting early response and immune-related adverse events (irAEs) is crucial for therapies with immune checkpoint inhibitors (ICI) in early-stage breast cancer (BC). This study evaluated serum markers at pre-treatment on-treatment, changes between timepoints women BC treated neoadjuvant chemotherapy plus ICI (anti-PD-1) or SD-101 (an immunomodulatory toll-like receptor 9 agonist) the I-SPY2 trial. Methods: Serum samples from HER2-negative (N=114) trial were collected...
A fundamental question in biology, central to our understanding of cancer and other pathologies, is determining how different cell types coordinate form maintain tissues. Recognizing the distinct features capabilities cells that compose these tissues critical. Unfortunately, complexity often hinders ability distinguish between neighboring and, turn, scrutinize their transcriptomes generate reliable tractable models for studying inherently biologies. We have recently introduced a novel method...
Effects from aging in single cells are heterogenous, whereas at the organ- and tissue-levels phenotypes tend to appear as stereotypical changes. The mammary epithelium is a bilayer of two major phenotypically functionally distinct cell lineages: luminal epithelial myoepithelial cells. Mammary epithelia exhibit substantial changes with age that merit attention because these putative cells-of-origin for breast cancers. We hypothesize effects impinge upon maintenance lineage fidelity increase...
Abstract Breast cancer largely dominates the global burden statistics; however, there are striking disparities in mortality rates across countries. While socioeconomic factors contribute to population-based differences mortality, they do not fully explain disparity among women of African ancestry (AA) and Arab (ArA) compared European (EA). In this study, we sought identify molecular that could provide insight into biology ancestry-associated clinical outcomes. We applied a unique approach...
Luminal epithelial cells in the breast gradually alter gene and protein expression with age, appearing to lose lineage-specificity by acquiring myoepithelial-like characteristics. We hypothesize that luminal lineage is particularly sensitive microenvironment changes, age-related changes cause altered cell phenotypes. To evaluate effects of different microenvironments on fidelity epigenetically regulated myoepithelial expression, we generated a set lineage-specific probes for genes are...
Abstract A majority of breast cancers (BC) are age-related and we seek to determine what cellular molecular changes occur in tissue with age that make women more susceptible cancer initiation. Immune-epithelial cell interactions important during mammary gland development the immune system plays an role BC progression. The composition human populations is known change peripheral blood Less about normal how their epithelia age. We quantified densities T cells, B macrophage subsets...
A robust breast cancer prevention strategy requires risk assessment biomarkers for early detection. We show that expression of ELF5, a transcription factor critical normal mammary development, is downregulated in luminal epithelia with age. DNA methylation the ELF5 promoter negatively correlated an age-dependent manner. Both and gene were used to build biological clocks estimate chronological ages epithelia. clock-based estimates age from average-risk women within three years Biological...
Triple-negative breast cancer (TNBC) accounts for ~15-20% of (BC) and has a higher rate early relapse mortality compared to other subtypes. The Chemokine (C-C motif) ligand 5 (CCL5) its signaling pathway have been linked TNBC. We aimed investigate the susceptibility prognostic implications genetic variation in CCL5 genes TNBC present study. characterized variants that six (CCND1, ZMIZ1, CASP8, NOTCH2, MAP3K21, HS6ST3) among 1,082 unrelated Tunisian subjects (544 BC patients, including 196...
Summary Aging causes molecular changes that manifest as stereotypical phenotypes yet aging-associated diseases progress only in certain individuals. At lineage-specific resolution, we show how stereotyped and variant responses are integrated mammary epithelia. Age-dependent directional gene expression DNA methylation (DNAm) occurred almost exclusively luminal cells implicated genome organizers SATB1 CTCF . DNAm were robust indicators of aging cells, either directly (anti-)correlated with or...
Age is the major risk factor in most carcinomas, yet little known about how proteomes change with age any human epithelium. We present comprehensive comprised of >9,000 total proteins and >15,000 phosphopeptides from normal primary mammary epithelia at lineage resolution ten women ranging 19 to 68 years. Data were quality controlled results biologically validated cell-based assays. Age-dependent protein signatures identified using differential expression analyses weighted co-expression...
Summary The role of germline genetics in shaping the tumor immune landscape is largely unknown. Using genotypes from >9,000 individuals Cancer Genome Atlas, we investigated association common and rare variants with 139 well-defined traits. Our analysis identified 10 traits significant heritability estimates, an additional 23 suggestive heritability, including estimates T-cell subset abundance interferon signaling. We performed genome-wide on 33 heritable loci associated at least one...